Automated API filling process

Abstract

An automated drug substance (DS) filling system is provided, comprising a plurality of pumps, each configured to fill a respective DS container; a plurality of weighing scales, each configured to measure a weight associated with each respective DS container; and a controller configured to cause each of the plurality of pumps to fill each respective DS container, monitor the weight associated with each respective DS container measured by the weighing scales, compare the weight associated with each respective DS container measured by the weighing scales to a threshold weight, and cause each of the plurality of pumps to stop filling each respective DS container based on the weight associated with their respective DS container reaching the threshold weight.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 319,675, entitled "AUTOMATED DRUG FILLING PROCESS," filed March 14, 2022, the entire disclosure of which is expressly incorporated herein by reference.

[0002] The present disclosure relates generally to filling of containers, and more specifically, to an automated drug substance (DS) filling system. [Background technology]

[0003] The background discussion provided herein is intended to generally present the context of the present disclosure. The inventors' work recited herein to the extent described in this Background section, and aspects of the description that would not qualify as prior art at the time of filing but for their work, are not expressly or implicitly admitted as prior art to the present disclosure.

[0004] Existing drug substance (DS) filling processes require significant time and effort for large-scale Good Manufacturing Practice (GMP) manufacturing. The standard existing DS filling method requires an operator to manually fill one container at a time, with the fill volume controlled by the operator manipulating a manual control valve while visually monitoring the scale reading to reach the desired mass. Summary of the Invention [Means for solving the problem]

[0005] In one aspect, an automated drug substance (DS) filling system is provided, the system comprising: a plurality of pumps, each pump configured to fill a respective DS container of a plurality of DS containers; a plurality of weighing scales, each weighing scale configured to measure a weight associated with each respective DS container of the plurality of DS containers; and a controller configured to cause each of the plurality of pumps to fill a respective DS container of the plurality of DS containers, monitor a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales, compare a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight, and cause each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the weight associated with its respective DS container reaching the threshold weight.

[0006] In another aspect, an automated DS filling system is provided, the system comprising: a plurality of pumps, each pump configured to fill a respective DS container of a plurality of DS containers; a plurality of sensors, each sensor configured to measure a DS flow rate from each of the plurality of pumps to each respective DS container of the plurality of DS containers; and a controller configured to cause each of the plurality of pumps to fill a respective DS container of the plurality of DS containers, monitor a fill volume from each of the plurality of pumps to each respective DS container of the plurality of DS containers, compare a fill volume associated with each respective DS container of the plurality of DS containers measured by each of the sensors to a threshold volume, and cause each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the fill volume associated with its respective DS container reaching the threshold volume.

[0007] In yet another aspect, a method of automated DS filling is provided, the method including: causing each of a plurality of pumps, by a controller, to fill each respective DS container of a plurality of DS containers; monitoring a weight associated with each respective DS container by a plurality of weighing scales, each weighing scale being associated with a respective DS container of the plurality of DS containers; comparing, by the controller, the weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight; and causing each of the plurality of pumps, by the controller, to stop filling each respective DS container of the plurality of DS containers based on the weight associated with its respective DS container reaching the threshold weight.

[0008] In yet another aspect, a method of automated DS filling is provided, the method including: causing each of a plurality of pumps, by a controller, to fill each respective DS container of a plurality of DS containers; monitoring a fill volume associated with each respective DS container by a plurality of sensors, each sensor associated with a respective DS container of the plurality of DS containers; comparing, by the controller, the fill volume associated with each respective DS container of the plurality of DS containers as measured by each of a plurality of weighing scales to a threshold volume; and causing each of the plurality of pumps, by the controller, to stop filling each respective DS container of the plurality of DS containers based on the fill volume associated with its respective DS container reaching the threshold volume. [Brief description of the drawings]

[0009] [Figure 1] 1 illustrates an exemplary piping and instrumentation diagram (P&ID) of an automated drug substance (DS) filling system according to certain examples provided herein. [Diagram 2] 1 illustrates an example weighing scale and controller that may be used in an automated DS filling system, according to certain embodiments provided herein. [Figure 3A]1 illustrates an example port for connecting a controller to a pump that may be used in an automated DS filling system, according to certain embodiments provided herein. [Figure 3B] 1 illustrates an example port for connecting a controller to a pump that may be used in an automated DS filling system, according to certain embodiments provided herein. [Figure 4] FIG. 1 illustrates an example of multiple DS containers connected by a tubing manifold to respective pumps via sealed sterile connections that may be used in an automated DS filling system according to some embodiments provided herein. [Diagram 5] 1 illustrates an exemplary tubing manifold that may be used in an automated DS filling system, according to certain examples provided herein. [Figure 6] FIG. 5 illustrates an example of multiple DS containers connected to respective pumps by tubing manifolds located on respective metering scales connected to respective controllers, such as may be used in an automated DS filling system, via sealed sterile connections as shown in FIG. [Figure 7] 1 shows a schematic diagram of an exemplary automated DS filling system according to certain embodiments provided herein. [Figure 8] 8 is a flow diagram of an example automatic dosing pump controlled DS filling method that may be used in the automatic DS filling system of FIG. 7, in accordance with certain embodiments provided herein. [Figure 9] 8 is a flow diagram of an example automatic scale controlled DS filling method that may be used in the automatic DS filling system of FIG. 7, in accordance with certain embodiments provided herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] overview The present disclosure provides an automated drug substance (DS) filling system in which DS containers are filled based on a target volume and / or a target mass or weight in a closed system. A piping and instrumentation diagram (P&ID) of an exemplary DS filling system provided herein is shown in FIG. 1. For example, in a dosing pump controlled DS filling system, DS containers may be filled to a target fill volume based on weighing values ​​from a pump head rotation sensor associated with each DS container, and in a scale controlled DS filling system, DS containers may be filled to a target mass or weight based on weighing values ​​from a weighing scale associated with each DS container.

[0011] In one embodiment, the innovative dosing pump controlled DS filling system disclosed herein automatically fills multiple (e.g., 3, 6, etc.) DS containers at a time near a target volume without the need for an operator to manually control the fill volume. The pump controlled DS filling system consists of multiple peristaltic dosing pumps that automatically transfer user programmable amounts of DS to the containers. A sterile tubing assembly splits the filling line into multiple streams and connects to multiple DS containers via sealed sterile connections, allowing multiple DS containers to be filled simultaneously. The user operates the device via a local keypad and display.

[0012] In another embodiment, the innovative scale-controlled DS filling system disclosed herein automatically fills multiple (e.g., 3, 6, etc.) DS containers at a time to a target mass without requiring an operator to monitor or manually control the fill volume. The scale-controlled DS filling system is comprised of multiple sets of equipment, each including a scale, a weighing terminal (Note: in some embodiments described herein, the "weighing terminal" may be referred to as a "controller"), and a peristaltic pump integrated to automatically transfer a user-programmable mass of DS to the container. An empty DS container is filled on a scale connected to a weighing terminal that is programmed to stop the peristaltic pump transferring the DS once the target weight is measured. A sterile tubing assembly splits the filling line into multiple streams and connects to multiple DS containers via sealed sterile connections, allowing multiple DS containers to be filled simultaneously. A user operates the equipment via a local keypad and display.

[0013] The Scale Controlled DS Filling System provides a fast, automated, consistent, and easy to use DS filling process. The Scale Controlled DS Filling System's ability to fill to target is not affected by varying process conditions such as upstream fill line pressure, setting it apart from filling systems that are controlled entirely by peristaltic dosing pumps. The ability to fill multiple containers at once significantly speeds up the filling process while allowing containers to be automatically filled to much closer to their maximum capacity with highly accurate and precise control, optimizing the use of single-use materials and labor associated with every fill and shipment.

[0014] In either case, the automated DS filling system provided herein provides a fast, automated DS filling process. The automated target filling control combined with the ability to fill multiple containers at once significantly reduces the time of the filling process. Furthermore, the use of pumps, rather than valves, to control the filling of each of the DS containers allows for increased speed and safety in the automated DS filling process provided herein. For example, compared to conventional systems that include a single pump (or multiple centrally controlled pumps) and utilize valves to regulate the flow rate to each container, the technique of the present invention prevents dangerous build-up of pressure and liquid in the system by using individualized pumps for each container. That is, if the operator chooses to stop filling by stopping the individualized pumps, the pumps stop drawing liquid from the source, so the chance of liquid or pressure exceeding the capacity of the tubing, which could cause the tubing to burst, is significantly reduced compared to a system in which the valves connected to the centrally controlled pumps are closed. Furthermore, the use of individualized pumps for each container allows the operator to stop filling at the individual container level more quickly and easily, if necessary, since there is no need to stop the pump and valve combination to stop filling.

[0015] The automated DS filling systems provided herein include benchtop devices designed to provide automatic, accurate, and reproducible filling of multiple DS bags (e.g., Sartorius Celsius® FTT bags) simultaneously. Specifically, the automated DS filling systems provided herein include multiple (e.g., three, six, etc.) sets of devices, each including a peristaltic pump (e.g., a Watson-Marlow 520Di peristaltic pump). In some embodiments, the pump uses a 505L pump head equipped with a 505LG track assembly.

[0016] For a dosing pump controlled DS system, the peristaltic dosing pump can be normalized offline to the process fill line pressure so that when connected to the fill line, a pump head rotation sensor can estimate the throughput of the pump. The normalized data can be used to calculate the pump head rotations required to transfer a target amount of DS (also referred to herein as the "threshold amount") to a vessel.

[0017] In the case of a scale-controlled DS filling system, each set of devices also includes a weighing scale. In addition, in the case of a scale-controlled DS filling system, each set of devices further includes a weighing terminal (e.g., Mettler Toledo PBK989 AB60 scale platform and Mettler Toledo IND-570 weighing terminal shown in FIG. 2). The devices in each set can be interconnected, allowing the weighing terminal to both read the scale and control the pump. In one embodiment, the pump is connected to the weighing terminal by a cable, e.g., a Turck cable with a 25-pin connector terminal, as shown in FIG. 3A and 3B.

[0018] In either case, a pair of empty DS bags are sterilely connected (e.g., via a sealed sterile connection) to each of the individual legs of the transfer assembly manifold via male and female connectors (e.g., Sartorius Opta® connectors, AseptiQuick® G connectors, etc.), for example, as shown in FIG. 4. For example, FIG. 5 illustrates an exemplary tubing manifold. Each of the legs of the transfer assembly manifold that are connected to the DS bags are mounted to an individual pump. The flow path to one of each pair of bags is set by the operator.

[0019] In the case of a dosing pump control DS system, each is allowed to run until the calculated number of pump head revolutions is completed.

[0020] For a scale-controlled DS filling system, as shown in FIG. 6, each pair of empty DS bags is placed on the weighing scale and each pump is allowed to run until a programmed target mass on the scale (also referred to herein as the "threshold mass" or "threshold weight") is measured, triggering the weighing terminal to stop the pump.

[0021] Although the techniques provided herein are discussed with respect to DS filling systems, the techniques described herein may in some embodiments be used with other types of filling, including media filling, or filling using other substances or liquids. Similarly, although the techniques provided herein are discussed with respect to filling DS containers, the techniques described herein may in some embodiments be used to fill other types of containers, such as carboys.

[0022] Example automatic DS filling system 7 is a schematic diagram of an example automated DS filling system 100, according to certain embodiments provided herein. The high-level architecture shown in FIG. 7 can include both hardware and software applications, as well as various data communication channels for communicating data between the various hardware and software components, as described below.

[0023] The automated DS filling system 100 may include a drug substance source 102 fluidly connected by a tubing manifold 104 via a sealed sterile connection to two or more pumps 106, each configured to fill a respective drug substance container 110. Specifically, the tubing manifold 104 may split the filling line from the drug substance source 102 into separate tubes for each drug substance container 110, and the pumps 106 for each drug substance container 110 may be located between the drug substance source 102 downstream from the split point and the drug substance container 110. Although three pumps 106 and three respective drug substance containers 110 are shown in FIG. 7, the automated DS filling system 100 may include any number of pumps 106 and respective drug substance containers 110.

[0024] When the automated DS filling system 100 is implemented as an automated dosing pump controlled DS filling system, each of the pumps 106 may be associated with a respective sensor 108 configured to measure the fill rate from the pump 106 to its respective DS container 110, either directly, e.g., via a flow rate sensor, or indirectly, e.g., via a pump head rotation sensor. For example, the pumps 106 may be peristaltic dosing pumps, and when connected to a fill line, the pump head rotation sensor 108 associated with each pump 106 may be normalized offline to the fill line pressure of the process such that the pump head rotation speed can be used to estimate throughput.

[0025] On the other hand, when the automated DS filling system 100 is implemented as an automated scale-controlled DS filling system, each of the DS containers 110 may be associated with a respective weighing scale 112 configured to monitor the weight or mass of the DS container 110.

[0026] The automated DS filling system 100 may include a controller 114 configured to control and communicate with each of the pumps 106, and either a sensor 108 associated with each pump 106 (in the case of an automated dosing pump controlled DS filling system) or a weighing scale 112 associated with the DS container 110 that each pump 106 is filling (in the case of an automated scale controlled DS filling system) via a respective wired or wireless connection. While FIG. 7 illustrates all of the pumps 106 (and their respective sensors 108 or weighing scales 112) being controlled by the same controller 114, in some embodiments, each of the pumps 106 (and their respective sensors 108 or weighing scales 112) may be controlled by a separate controller 114. Additionally, while FIG. 7 illustrates that the controller 114 is separate from the pumps 106, in some embodiments, the separate controller 114 may be located within or attached to each of the pumps 106.

[0027] The controller 114 may include or communicate with a user interface 116, through which the controller 114 may receive input from or provide information to a user. The controller 114 may further include one or more processors 118 and a memory 120 (e.g., volatile memory, non-volatile memory). The memory 120 may be accessible by the one or more processors 118 (e.g., via a memory controller). The one or more processors 118 may interact with the memory 120, for example, to retrieve computer-readable instructions stored in the memory 120. The computer-readable instructions stored in the memory 120 may cause the one or more processors 118 of the controller 114 to execute one or more applications. In particular, the computer readable instructions stored in the memory 120 may include instructions to cause the controller 114 to control each pump 106 to begin filling its respective DS container 110 and to monitor either the fill volume associated with each DS container 110 using data received from a sensor 108 associated with the pump 106 that is filling the DS container 110 (in the case of an automatic dosing pump controlled DS filling system) or the weight or mass associated with each DS container 110 using data received from a weighing scale 112 associated with the DS container 110 (in the case of an automatic scale controlled DS filling system). The computer readable instructions stored in the memory 120 may further include instructions to cause the controller 114 to stop filling each pump 106 (in some cases, independently of the other pumps 106) based on a target or threshold that the DS container 110 associated with the pump 106 is reaching. In the case of an automatic dosing pump controlled DS filling system, the target or threshold is a target fill volume or a threshold fill volume, and in the case of an automatic scale controlled DS filling system, the target or threshold is a target or threshold weight or mass.

[0028] In some embodiments, the computer readable instructions stored in memory 120 can further include instructions for receiving input from a user, e.g., via the user interface 116, indicating a target or threshold quantity, mass, or weight of each DS container 110. Additionally, in some embodiments, the computer readable instructions stored in memory 120 can further include instructions for providing an audio or visual alert to the user, e.g., via the user interface 116, an alert indicating that a target or threshold quantity, mass, or weight of a DS container 110 has been reached.

[0029] Further, in some embodiments, the computer readable instructions stored in memory 120 may include instructions for performing any of the steps of method 200, described in more detail below with respect to FIG. 8, and / or method 300, described in more detail below with respect to FIG. 9.

[0030] Exemplary Automatic Dosing Pump Controlled DS Filling Method Figure 8 is a flow diagram of an example automatic dosing pump controlled DS filling method 200 that may be used in the automatic DS filling system 100 of Figure 7, according to certain embodiments provided herein. One or more steps of method 200 may be implemented as a set of instructions stored on a computer-readable memory (e.g., memory 120) and executable on one or more processors (e.g., processor 118).

[0031] The method 200 can begin, for example, when two or more pumps 106 are controlled by the controller 114 to each begin filling (block 202) a respective DS container 110. In some embodiments, each of the pumps 106 can be controlled by an individual controller 114, while in other embodiments, multiple pumps 106 can be controlled by the same controller 114. In either case, the pumps 106 can be controlled separately from one another to fill the DS containers 110, e.g., to begin at different times, different fill rates, etc., in some embodiments.

[0032] The fill volume of the DS container 110 associated with each of the pumps 106 may be monitored (block 204) by a respective sensor 108 associated with each pump 106. For example, the sensor may be a pump head rotation sensor, and the fill volume of a given pump 106 may be monitored based on the pump head rotation number detected by the sensor 108 associated with that pump 106. That is, a peristaltic dosing pump, when connected to a fill line, may be normalized offline to the fill line pressure of the process such that the pump head rotation sensor may estimate the throughput of the pump. The normalized data may be used to calculate the pump head rotations required to transfer a target amount (also referred to herein as a "threshold amount") of DS to the container.

[0033] In some embodiments, the method 200 can include receiving an indication of a target or threshold amount requested by a user, for example, via the user interface 116. In some embodiments, the target or threshold amount for each DS container 110 can be the same, while in other embodiments, the target or threshold amount for one of the DS containers 110 can be different from another of the DS containers 110 (e.g., based on DS containers 110 of different sizes).

[0034] The fill volume of the DS reservoir 110 associated with each pump 106 (eg, calculated based on pump head rotation speed) may be compared (block 206) to a threshold volume, for example, by the controller 114.

[0035] Each pump 106 may be controlled to stop filling its respective DS container 110 (block 208) based on the fill volume of the DS container 110 reaching a threshold volume. As noted above, the pumps 106 may be controlled separately from one another to stop filling the DS containers 110 based on, for example, target or threshold volumes being reached for each different DS container 110 and / or at different times.

[0036] In some embodiments, the method 200 can further include generating (e.g., by the controller 114) a respective alert when each DS container 110 reaches a threshold or target volume, for example, as indicated via the user interface 116.

[0037] Exemplary Auto-Scale Control DS Filling Method Figure 9 is a flow diagram of an example automatic scale controlled DS filling method 300 that may be used in the automatic DS filling system 100 of Figure 7, according to certain embodiments provided herein. One or more steps of the method 300 may be implemented as a set of instructions stored on a computer-readable memory (e.g., memory 120) and executable on one or more processors (e.g., processor 118).

[0038] The method 300 can begin, for example, when two or more pumps 106 are controlled by the controller 114 to each begin filling (block 302) a respective DS container 110. In some embodiments, each of the pumps 106 can be controlled by an individual controller 114, while in other embodiments, multiple pumps 106 can be controlled by the same controller 114. In either case, the pumps 106 can be controlled separately from one another to fill the DS containers 110 in some embodiments, e.g., to begin at different times, at different fill rates, etc.

[0039] The weight or mass of each of the DS vessels 110 may be monitored (block 304 ) by a weighing scale 112 associated with each pump 106 .

[0040] The weight or mass of each DS container 110, as measured by a weighing scale 112 associated with the DS container 110, may be compared (block 306), for example, by the controller 114, to a threshold weight or mass. In some embodiments, the method 300 may include receiving an indication of a threshold weight or mass (or target weight or mass) requested by a user, for example, via the user interface 116. In some embodiments, the threshold weight or mass (or target weight or mass) for each DS container 110 may be the same, while in other embodiments, the threshold weight or mass (or target weight or mass) for one of the DS containers 110 may be different from another one of the DS containers 110 (e.g., based on DS containers 110 of different sizes).

[0041] In either case, each pump 106 may be controlled, for example, by the controller 114, to stop filling its respective DS container 110 based on the weight or mass of the DS container 110 reaching a threshold weight or mass (block 308). As noted above, the pumps 106 may be controlled separately from one another to stop filling the DS containers 110 based, for example, on threshold weights or masses (or target weights or masses) being reached for each different DS container 110 and / or at different times.

[0042] In some embodiments, the method 300 can further include generating (e.g., by the controller 114) a respective alert, indicated, for example, via the user interface 116, when each DS container 110 reaches a threshold weight or mass (or target weight or mass).

[0043] Additional considerations The following additional considerations also apply to the above description: Throughout this specification, multiple instances may implement components, operations, or structures described as a single instance. Although individual operations of one or more methods are illustrated or described as separate operations, one or more of the individual operations may be performed simultaneously, and the operations need not be performed in the order illustrated. Structures and functions shown as separate elements in multiple configuration examples may be implemented as combined structures or elements. Similarly, structures and functions shown as a single element may be implemented as separate elements. These and other variations, modifications, additions, and improvements are within the scope of the subject matter of this disclosure.

[0044] Additionally, certain embodiments are described herein as including logic or a number of components, modules, or mechanisms. A module may constitute either a software module (e.g., code stored on a machine-readable medium) or a hardware module. A hardware module is a tangible unit that can perform certain operations and may be configured or arranged in a particular manner. In an exemplary embodiment, one or more computer systems (e.g., standalone, client, or server computer systems) or one or more hardware modules of a computer system (e.g., a processor or processors) may be configured as a hardware module that operates by software (e.g., an application or application portions) to perform certain operations as described herein.

[0045] A hardware module may include dedicated circuitry or logic that is permanently configured (e.g., as a dedicated processor such as a field programmable gate array (FPGA) or application specific integrated circuit (ASIC)) to perform certain operations. A hardware module may also include programmable logic or circuitry that is temporarily configured by software to perform certain operations (e.g., contained within a general purpose processor or other programmable processor). It will be appreciated that the decision to implement a hardware module in dedicated and permanently configured circuitry or temporarily configured circuitry (e.g., configured by software) may be made based on cost and time considerations.

[0046] Thus, the term hardware should be understood to encompass tangible entities that are physically constructed and permanently configured (e.g., hardwired) or temporarily configured (e.g., programmed) to operate in a particular manner or perform particular operations as described herein. When considering embodiments in which hardware modules are temporarily configured (e.g., programmed), each hardware module need not be configured or instantiated at any instance in time. For example, if the hardware modules include a general-purpose processor configured with software, the general-purpose processor may be configured as different hardware modules at different times. Thus, the software may configure the processor, for example, to be a component of a particular hardware module at one instance and a component of a different hardware module at a different instance.

[0047] Hardware and software modules can provide and receive information to and from other hardware and / or software modules. Thus, the described hardware modules may be considered to be communicatively coupled. When multiple such hardware or software modules are present simultaneously, communication may be achieved through signal transmission (e.g., via appropriate circuits and buses) connecting the hardware or software modules. In embodiments in which multiple hardware or software modules are configured or instantiated at different times, communication between such hardware or software modules may be realized, for example, through storage and retrieval of information in memory structures accessible to the multiple hardware or software modules. For example, one hardware or software module may perform an operation and store the output of that operation in a memory device to which it is communicatively coupled. An additional hardware or software module may then later access the memory device to retrieve and process the stored output. Hardware and software modules may initiate communication with input or output devices and may operate on resources (e.g., a set of information).

[0048] Various operations of the example methods described herein may be performed, at least in part, by one or more processors that are temporarily or permanently configured (e.g., by software) to perform the associated operations. Whether temporarily or permanently configured, such processors may comprise processor-implemented modules that operate to perform one or more operations or functions. Modules referred to herein may include processor-implemented modules in some example embodiments.

[0049] Similarly, the methods or routines described herein may be at least partially processor-implemented. For example, at least some of the operations of a method may be executed by one or more processors or processor-implemented hardware modules. The execution of certain operations may be distributed among one or more processors and may reside within a single machine as well as spread across multiple machines. In some exemplary embodiments, the processor may be located in a single location (e.g., in a home environment, in an office environment, or as a server farm), while in other embodiments the processor may be distributed across multiple locations.

[0050] The one or more processors may also operate to support execution of related operations within a "cloud computing" environment or as SaaS. For example, as noted above, at least some of the operations may be performed by a collection of computers (as examples of machines that include a processor), which are accessible over a network (e.g., the Internet) and via one or more suitable interfaces (e.g., APIs).

[0051] Performance of certain operations may be distributed among one or more processors and may reside within a single machine as well as be spread across multiple machines. In some exemplary embodiments, one or more processors or processor-implemented modules may be located in a single geographic location (e.g., in a home environment, an office environment, or a server farm). In other exemplary embodiments, one or more processors or processor-implemented modules may be distributed across multiple geographic locations.

[0052] Some portions of this specification are presented in terms of algorithms or symbolic representations of operations on data stored as bits or binary digital signals in a machine memory (e.g., computer memory). These algorithms or symbolic representations are examples of techniques used by those skilled in the data processing arts to convey the substance of their work to others skilled in the art. An "algorithm" or "routine" as used herein is a self-consistent sequence of operations or similar processes that lead to a desired result. In this context, algorithms, routines, and operations involve physical manipulations of physical quantities. Typically, although not necessarily, such quantities can take the form of electrical, magnetic, or optical signals capable of being stored, accessed, transmitted, combined, compared, or otherwise manipulated by a machine. It is sometimes convenient, primarily for reasons of common usage, to refer to such signals using words such as "data," "contents," "bits," "values," "elements," "symbols," "characters," "terms," ​​"numbers," "numeric values," and the like. However, these words are merely convenient labels and should be associated with the appropriate physical quantities.

[0053] Unless otherwise noted, descriptions herein using words such as "processing," "computing," "calculating," "determining," "presenting," "displaying," and the like may refer to machine (e.g., computer) operations or processes that manipulate or transform data represented as physical (e.g., electronic, magnetic, or optical) quantities in one or more memories (e.g., volatile memory, non-volatile memory, or a combination thereof), registers, or other machine components to receive, store, transmit, or display information.

[0054] As used herein, a reference to "one embodiment" or "an embodiment" means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment.

[0055] Some embodiments may be described using the terms "coupled" and "connected," along with their derivatives. For example, some embodiments may be described using the term "coupled" to indicate that two or more elements are in direct physical or electrical contact with each other. However, the term "coupled" may also mean that two or more elements are not in direct contact with each other, but still co-operate or interact with each other. The embodiments are not limited in this context.

[0056] As used herein, the terms "comprise," "includes," "includes," "including," "having," "having" or any other variation thereof are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Furthermore, unless expressly stated to the contrary, "or" refers to an inclusive or rather than an exclusive or. For example, a condition A or B is satisfied by any one of A being true (or present) and B being false (or absent), A being false (or absent) and B being true (or present), or both A and B being true (or present).

[0057] Additionally, the use of "a" or "an" is employed to describe elements and components of embodiments herein. This is done merely for convenience and to give a general sense of the description. This description should be read to include one or at least one, and the singular also includes the plural, unless otherwise clearly meant.

[0058] Upon perusal of this disclosure, those skilled in the art will appreciate further alternative structures and functional designs through the principles disclosed herein. Thus, while particular embodiments and applications have been illustrated and described, it should be understood that the disclosed embodiments are not limited to the precise structures and elements disclosed herein. Various modifications, changes and variations, which will be apparent to those skilled in the art, may be made to the arrangement, operation and details of the methods and apparatus disclosed herein without departing from the concept and scope defined in the appended claims.

[0059] Aspects 1. An automated drug substance (DS) filling system comprising a plurality of pumps, each pump configured to fill a respective DS container of a plurality of DS containers; a plurality of weighing scales, each weighing scale configured to measure a weight associated with each respective DS container of the plurality of DS containers; and a controller configured to cause each of the plurality of pumps to fill a respective DS container of the plurality of DS containers, monitor a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales, compare a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight, and cause each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the weight associated with its respective DS container reaching the threshold weight.

[0060] 2. The automated DS filling system of embodiment 1 further comprises a tubing manifold configured to connect a filling line to each of the plurality of pumps via a sealed sterile connection.

[0061] 3. The automated DS filling system of any one of aspects 1 or 2, further comprising a user interface, and the controller is further configured to receive an indication of the threshold weight as an input via the user interface.

[0062] 4. The automated DS filling system of any one of aspects 1-3, wherein the controller is further configured to individually control each of the plurality of pumps to stop filling of each respective DS container.

[0063] 5. In the automated DS filling system of any one of aspects 1-4, the controller is further configured to generate a respective alert based on a weight associated with each DS container reaching the threshold weight.

[0064] 6. An automated drug substance (DS) filling system comprising: a plurality of pumps, each pump configured to fill a respective DS container of a plurality of DS containers; a tubing manifold configured to connect a filling line from a DS source to each of the plurality of pumps via a sealed sterile connection; a plurality of sensors, each sensor configured to measure a DS flow rate from each of the plurality of pumps to each respective DS container of the plurality of DS containers; and a controller configured to cause each of the plurality of pumps to fill a respective DS container of the plurality of DS containers, monitor a fill volume from each of the plurality of pumps to each respective DS container of the plurality of DS containers, compare a fill volume associated with each respective DS container of the plurality of DS containers measured by each of the sensors to a threshold volume, and cause each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the fill volume associated with its respective DS container reaching the threshold volume.

[0065] 7. In the automatic DS filling system of embodiment 6, the sensor is a pump head rotation sensor.

[0066] 8. The automated DS filling system of any one of aspects 6 or 7, further comprising a user interface, and the controller is further configured to receive an indication of the threshold amount as input via the user interface.

[0067] 9. The automatic DS filling system of any one of embodiments 6-8, wherein the controller is further configured to individually control each of the plurality of pumps to stop filling of each respective DS container.

[0068] 10. In the automated DS filling system of any one of aspects 6-9, the controller is further configured to generate a respective alert based on a fill volume associated with each DS container reaching a threshold volume.

[0069] 11. A method of automated drug substance (DS) filling includes: causing each of a plurality of pumps, by a controller, to fill a respective DS container of a plurality of DS containers, each of the plurality of pumps being connected by a tubing manifold via a sealed sterile connection to a filling line from a DS source; monitoring a weight associated with each respective DS container by a plurality of weighing scales, each weighing scale being associated with a respective DS container of the plurality of DS containers; comparing, by the controller, a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight; and causing each of the plurality of pumps, by the controller, to stop filling each respective DS container of the plurality of DS containers based on the weight associated with their respective DS container reaching the threshold amount.

[0070] 12. The automatic DS filling method of embodiment 11 further includes receiving, by the controller, an indication of the threshold weight as input via the user interface.

[0071] 13. In the automatic DS filling method of any one of aspects 11 or 12, causing each of the plurality of pumps, by the controller, to stop filling each respective DS container includes individually controlling each of the plurality of pumps to stop filling each respective DS container.

[0072] 14. The automated DS filling method of any one of aspects 11-13, further comprising generating, by the controller, a respective alert based on a weight associated with each DS container reaching the threshold amount.

[0073] 15. A method of automated drug substance (DS) filling includes: causing each of a plurality of pumps, by a controller, to fill each respective DS container of a plurality of DS containers; monitoring a fill amount associated with each respective DS container by a plurality of sensors, each sensor associated with a respective DS container of the plurality of DS containers; comparing, by the controller, a fill amount associated with each respective DS container of the plurality of DS containers as measured by each of a plurality of weighing scales to a threshold amount; and causing each of the plurality of pumps, by the controller, to stop filling each respective DS container of the plurality of DS containers based on the fill amount associated with its respective DS container reaching the threshold amount.

[0074] 16. In the automatic DS filling method of embodiment 15, the plurality of sensors are pump head rotation sensors.

[0075] 17. The automatic DS filling method of any one of aspects 15 or 16 further includes receiving, by the controller, an indication of the threshold amount as input via a user interface.

[0076] 18. In the automatic DS filling method of any one of embodiments 15 to 17, causing each of the plurality of pumps to stop filling each respective DS container by the controller includes individually controlling each of the plurality of pumps to stop filling each respective DS container.

[0077] 19. The automatic DS filling method of any one of aspects 15-18, further including generating, by the controller, a respective alert based on a fill volume associated with each DS container reaching the threshold volume.

Claims

1. 1. An automated drug substance (DS) filling system, comprising: a plurality of pumps, each pump configured to fill a respective DS container of the plurality of DS containers; a plurality of weighing scales, each weighing scale configured to measure a weight associated with each respective DS container of the plurality of containers; A controller, causing each of the plurality of pumps to fill a respective DS container of the plurality of containers; monitoring the weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales; comparing the weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight; a controller configured to cause each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the weight associated with the respective DS container reaching the threshold weight; A system comprising:

2. 10. The automated DS filling system of claim 1, further comprising a tubing manifold configured to connect a filling line from a DS source to each of the plurality of pumps via a sealed sterile connection.

3. The automated DS filling system of claim 1 , further comprising a user interface, the controller being further configured to receive an indication of the threshold weight as an input via the user interface.

4. The automated DS filling system of claim 1 , wherein the controller is further configured to individually control each of the plurality of pumps to stop filling each respective DS container.

5. The automated DS filling system of claim 1 , wherein the controller is further configured to generate a respective alert based on the weight associated with each DS container reaching the threshold weight.

6. 1. An automated drug substance (DS) filling system, comprising: a plurality of pumps, each pump configured to fill a respective DS container of the plurality of DS containers; a tubing manifold configured to connect a fill line from a DS source to each of the plurality of pumps via a sealed sterile connection; a plurality of sensors, each sensor configured to measure a DS flow rate from each of the plurality of pumps to each respective DS vessel of the plurality of DS vessels; A controller, causing each of the plurality of pumps to fill a respective DS container of the plurality of containers; monitoring the fill rate of each of the plurality of pumps into each respective DS container of the plurality of DS containers; comparing a fill amount associated with each respective DS container of the plurality of DS containers measured by each of the sensors to a threshold amount; a controller that causes each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the fill volume associated with the respective DS container reaching the threshold volume; A system comprising:

7. 7. The automated DS filling system of claim 6, wherein the sensor is a pump head rotation sensor.

8. The automated DS filling system of claim 6 , further comprising a user interface, the controller being further configured to receive an indication of the threshold amount as an input via the user interface.

9. The automated DS filling system of claim 6 , wherein the controller is further configured to individually control each of the plurality of pumps to stop filling each respective DS container.

10. The automated DS filling system of claim 6 , wherein the controller is further configured to generate a respective alert based on the fill volume associated with each DS container reaching the threshold volume.

11. 1. An automated drug substance (DS) filling method, comprising: causing each of a plurality of pumps, by a controller, to fill a respective DS container of a plurality of DS containers, each of the plurality of pumps being connected to a fill line from a DS source using a tubing manifold via a sealed sterile connection; monitoring a weight associated with each respective DS container with a plurality of weighing scales, each weighing scale associated with a respective DS container of the plurality of DS containers; comparing, by the controller, a weight associated with each respective DS container of the plurality of DS containers measured by each of the plurality of weighing scales to a threshold weight; causing each of the plurality of pumps, by the controller, to stop filling each respective DS container of the plurality of DS containers based on the weight associated with the respective DS container reaching the threshold weight; The method includes:

12. 12. The automated DS filling method of claim 11, further comprising receiving an indication of the threshold weight as input via a user interface.

13. 12. The automated DS filling method of claim 11, wherein causing each of the plurality of pumps by the controller to stop filling each respective DS container comprises individually controlling each of the plurality of pumps to stop filling each respective DS container.

14. 12. The automated DS filling method of claim 11, further comprising generating, by the controller, a respective alert based on the weight associated with each DS container reaching the threshold weight.

15. 1. An automated drug substance (DS) filling method, comprising: causing each of the plurality of pumps to respectively fill a respective DS container of the plurality of DS containers, by the controller; monitoring a fill volume associated with each respective DS container with a plurality of sensors, each sensor associated with a respective DS container of the plurality of DS containers; comparing, by the controller, the fill amount associated with each respective DS container of the plurality of DS containers measured by each of a plurality of weighing scales to a threshold amount; causing each of the plurality of pumps to stop filling each respective DS container of the plurality of DS containers based on the fill volume associated with the respective DS container reaching the threshold volume, The method includes:

16. 16. The automated DS filling method of claim 15, wherein the plurality of sensors are pump head rotation sensors.

17. 16. The method of claim 15, further comprising receiving, by the controller, an indication of the threshold amount as an input via a user interface.

18. 16. The automated DS filling method of claim 15, wherein causing each of the plurality of pumps to stop filling each respective DS container by the controller comprises individually controlling each of the plurality of pumps to stop filling each respective DS container.

19. 16. The automated DS filling method of claim 15, further comprising generating, by the controller, a respective alert based on the fill volume associated with each DS container reaching the threshold volume.

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